Human podocalyxin alternative-spliced forms and uses thereof

Abstract

The present invention provides a method for diagnosing and detecting cancer. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in cancer (podocalyxin) and antibodies that bind podocalyxins. The present invention provides that podocalyxins are used as targets for screening agents that modulate podocalyxin activities. Further the present invention provides methods for treating diseases associated with podocalyxin expression.

1 . An isolated protein consisting of an amino acid sequence selected from the group consisting of: 
 (a) an amino acid sequence shown in SEQ ID NO:4;    (b) an amino acid sequence shown in SEQ ID NO:5;    (c) an amino acid sequence shown in SEQ ID NO:6;    (d) a fragment of an amino acid sequence shown in SEQ ID NO:4, wherein said fragment comprises at least 10 contiguous amino acids;    (e) a fragment of an amino acid sequence shown in SEQ ID NO:5, wherein said fragment comprises at least 10 contiguous amino acids; and    (f) a fragment of an amino acid sequence shown in SEQ ID NO:6, wherein said fragment comprises at least 10 contiguous amino acids.    
     
     
         2 . An isolated protein comprising an amino acid sequence selected from the group consisting of: 
 (a) an amino acid sequence shown in SEQ ID NO:4;    (b) an amino acid sequence shown in SEQ ID NO:5;    (c) an amino acid sequence shown in SEQ ID NO:6;    (d) a fragment of an amino acid sequence shown in SEQ ID NO:4, wherein said fragment comprises at least 10 contiguous amino acids;    (e) a fragment of an amino acid sequence shown in SEQ ID NO:5, wherein said fragment comprises at least 10 contiguous amino acids; and    (f) a fragment of an amino acid sequence shown in SEQ ID NO:6, wherein said fragment comprises at least 10 contiguous amino acids;    
     
     
         3 . An isolated antibody that selectively binds to a protein of  claim 2 .  
     
     
         4 . An isolated nucleic acid molecule consisting of a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence of SEQ ID NO: 1;    (b) a nucleotide sequence of SEQ ID NO: 2;    (c) a nucleotide sequence of SEQ ID NO: 3;    (d) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:4;    (e) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:5;    (f) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:6;    (g) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:4, wherein said fragment comprises at least 10 contiguous amino acids;    (h) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:5, wherein said fragment comprises at least 10 contiguous amino acids;    (i) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:6, wherein said fragment comprises at least 10 contiguous amino acids; and    (j) a nucleotide sequence that is the complement of a nucleotide sequence of (a)-(i).    
     
     
         5 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence of SEQ ID NO: 1;    (b) a nucleotide sequence of SEQ ID NO: 2;    (c) a nucleotide sequence of SEQ ID NO: 3;    (d) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:4;    (e) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:5;    (f) a nucleotide sequence that encodes an amino acid sequence shown in SEQ ID NO:6;    (g) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:4, wherein said fragment comprises at least 10 contiguous amino acids;    (h) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:5, wherein said fragment comprises at least 10 contiguous amino acids;    (i) a nucleotide sequence that encodes a fragment of an amino acid sequence shown in SEQ ID NO:6, wherein said fragment comprises at least 10 contiguous amino acids; and    (j) a nucleotide sequence that is the complement of a nucleotide sequence of (a)-(i).    
     
     
         6 . A transgenic non-human animal comprising a nucleic acid molecule of  claim 5 .  
     
     
         7 . A nucleic acid vector comprising a nucleic acid molecule of  claim 5 .  
     
     
         8 . A host cell containing the vector of  claim 7 .  
     
     
         9 . A method for producing any of the peptides of  claim 1  comprising introducing a nucleotide sequence encoding any of the amino acid sequences in (a)-(f) into a host cell, and culturing the host cell under conditions in which the peptides are expressed from the nucleotide sequence.  
     
     
         10 . A method for producing any of the peptides of  claim 2  comprising introducing a nucleotide sequence encoding any of the amino acid sequences in (a)-(f) into a host cell, and culturing the host cell under conditions in which the peptides are expressed from the nucleotide sequence.  
     
     
         11 . A method for detecting the presence of any of the peptides of  claim 2  in a sample, said method comprising contacting said sample with a detection agent that specifically allows detection of the presence of the peptide in the sample and then detecting the presence of the peptide.  
     
     
         12 . A method for detecting the presence of a nucleic acid molecule of  claim 5  in a sample, said method comprising contacting the sample with an oligonucleotide that hybridizes to said nucleic acid molecule under stringent conditions and determining whether the oligonucleotide binds to said nucleic acid molecule in the sample.  
     
     
         13 . A method for identifying a modulator of a peptide of  claim 2 , said method comprising contacting said peptide with an agent and determining if said agent has modulated the function or activity of said peptide.  
     
     
         14 . The method of  claim 13 , wherein said agent is administered to a host cell comprising an expression vector that expresses said peptide.  
     
     
         15 . A method for identifying an agent that binds to any of the peptides of  claim 2 , said method comprising contacting the peptide with an agent and assaying the contacted mixture to determine whether a complex is formed with the agent bound to the peptide.  
     
     
         16 . A pharmaceutical composition comprising an agent identified by the method of  claim 15  and a pharmaceutically acceptable carrier therefor.  
     
     
         17 . A method for treating a disease or condition mediated by a human podocalyxin protein, said method comprising administering to a patient a pharmaceutically effective amount of an agent identified by the method of  claim 15 .  
     
     
         18 . A method for identifying a modulator of the expression of a peptide of  claim 2 , said method comprising contacting a cell expressing said peptide with an agent, and determining if said agent has modulated the expression of said peptide.